Advance of sporadic Alzheimer's disease animal models

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti-AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti-AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti-AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti-AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti-AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.     

Memory impairment and awareness of memory deficits in early-stage Alzheimer's disease

In addition to their memory impairment, individuals with Alzheimer's disease (AD) often suffer from deficits in self-awareness. Awareness of memory deficits or metamemory is a multifaceted function, comprising on-line self-monitoring, generalized self-beliefs of memory efficacy, and generalized knowledge about memory functions. Awareness of memory problems in early-stage AD is a matter of clinical importance from a humanistic point of view, because higher levels of awareness may be associated with better future outcomes. Current methods of measuring awareness tend to fall into two categories, i.e., to introduce a questionnaire assessing patient/caregiver discrepancies; or to ask a patient to prospectively predict or retrospectively postdict their own memory performances. Characteristics of each measure as well as relationship between the two measures were discussed. For the performance prediction/postdiction paradigm, we used recognition memory of auditory verbal learning tests and awareness of memory deficits were examined in 24 individuals with early-stage AD. In addition to their significantly impaired recognition memory, individuals with AD displayed underawareness of memory deficits even at this early stage. They retrospectively overestimated memory performance after actual performance, but appeared to benefit from feedback and displayed intact on-line awareness of memory dysfunction, leading to normal prediction of the second session. However, individuals with AD again failed to retrospectively incorporate incidents of memory failure into generalized self-belief systems. Brain/behavior correlational analyses suggest that the prefrontal cortex and posterior dorsomedial regions including the precuneus may be involved in self-awareness.     

Face-name memory in Alzheimer's disease

Alzheimer's disease (AD) affects face-name memory, the ability to recognize faces and recall names. Remembering face and name requires a sophisticated cognitive process because of the complexity and similarity among faces and also because of their arbitrary association with names. Assessments of face-name memory can measure episodic and semantic memory performance and are useful for early detection of AD. Improving face-name memory is possible through cognitive interventions targeted to promote procedural memory, which is often preserved until the late stage of AD. This article describes a conceptual model, assessment tools, and strategies for improving face-name memory in persons with AD.     

阿尔茨海默病转基因小鼠早期记忆功能障碍与氧化应激损伤关系的实验研究

Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P ＜0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P ＜0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P ＜0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P ＜ 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P ＜ 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P ＜ 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P ＜ 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP/PS1 mice, suggesting that protein carbonylation caused by oxidative stress might play an important role in the development of memory impairment in the early stage of Alzheimer's disease.     

阿尔茨海默病转基因小鼠早期记忆功能障碍与氧化应激损伤关系的实验研究

目的 观察转APP/PS1基因阿尔茨海默病(AD)小鼠(APP/PS1小鼠)早期空间学习记忆功能及相关氧化应激反应指标的变化,并探讨它们之间的相关性.方法 应用Morris水迷宫评定APP/PS1小鼠及相应野生型(WT)小鼠的空间学习记忆功能,采用ELISA方法检测脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性以及丙二醛(MDA)和蛋白质羰基的含量,并进行相关性分析.结果 2组小鼠的空间学习能力无明显差异(P＞0.05),而APP/PS1小鼠在目标象限(定位航行实验中平台所置第二象限)中航行时间占总时间的百分比(29.02±4.27)%较WT小鼠(47.39±6.01)%显著下降(t=0.000,P＜0.05),APP/PS1小鼠在目标象限中航行路程占总路程的百分比(28.85±3.77)%较WT小鼠(46.70±5.60)%也显著下降(t=0.000,P＜0.05),提示APP/PS1小鼠的空间记忆功能较WT小鼠显著下降.2组小鼠脑组织中的MDA含量、SOD和GSH-PX活性均无明显差异(P均＞0.05),而APP/PS1小鼠脑组织中的蛋白质羰基含量(2.67±0.19)较WT小鼠(2.38±0.15)显著增加(t=0.0088,P＜0.05).相关性分析表明:APP/PS1小鼠蛋白质羰基含量与目标象限航行时间百分比呈显著负性相关(r=-0.639,P＜0.05),APP/PS1小鼠蛋白质羰基含量与目标象限航行路程百分比呈显著负性相关(r=-0.636,P＜0.05).结论 APP/PS1小鼠早期空间记忆功能损害与脑组织中的蛋白质羰基含量升高呈负性相关,提示氧化应激导致的蛋白质羰基化在AD早期记忆损害发病过程中具有重要作用.

Abstract：

Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P ＜0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P ＜0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P ＜0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P ＜ 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P ＜ 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P ＜ 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P ＜ 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP/PS1 mice, suggesting that protein carbonylation caused by oxidative stress might play an important role in the development of memory impairment in the early stage of Alzheimer's disease.     

Verbal episodic memory impairment in Alzheimer's disease: a combined structural and functional MRI study

Anatomical and functional MRI images were acquired in a group of healthy elderly subjects (n = 11) and a group of patients diagnosed with probable Alzheimer's disease, from mild to moderate severity (n = 8). During functional sessions, verbal episodic Encoding and Recognition tasks were presented to subjects. Both groups were compared in terms of gray matter volume and cerebral activation. Furthermore, in the AD group, correlations between hippocampal gray matter volume and whole-brain activations were examined. When compared to healthy controls, AD patients presented significant gray matter atrophy as well as reduced activations during Encoding and Recognition in the medial temporal lobes and inferior parietal/superior temporal associative areas. In the same regions, the fMRI activity elicited by the Recognition task was positively correlated with hippocampal gray matter volume. Moreover, an increase of left prefrontal activity during Encoding and Recognition was observed in AD patients relative to controls and was correlated with memory performance. This additional activity elicited by episodic memory processes was not found to correlate with the degree of medial temporal atrophy in our group of patients. Our study shows that function in brain regions critical to episodic memory is altered in AD. During episodic Recognition, these functional changes may closely correlate with the progressive structural changes observed in the hippocampal region.     

工作记忆与Alzheimer病工作记忆障碍的功能磁共振成像研究

工作记忆属于短时记忆的一种,在人类记忆过程中起重要作用.老年性痴呆(Alzheimer's disease,AD)是一种以记忆缺陷为主要临床表现的脑变性疾病.本文就功能磁共振成像在工作记忆及AD工作记忆缺陷方面的研究进展进行综述.     

Using Reiki to decrease memory and behavior problems in mild cognitive impairment and mild Alzheimer's disease

OBJECTIVES: This empirical study explored the efficacy of using Reiki treatment to improve memory and behavior deficiencies in patients with mild cognitive impairment or mild Alzheimer's disease. Reiki is an ancient hands-on healing technique reputedly developed in Tibet 2500 years ago. DESIGN: This study was a quasi-experimental study comparing pre- and post-test scores of the Annotated Mini-Mental State Examination (AMMSE) and Revised Memory and Behavior Problems Checklist (RMBPC) after four weekly treatments of Reiki to a control group. SETTINGS/LOCATION: The participants were treated at a facility provided by the Pleasant Point Health Center on the Passamaquoddy Indian Reservation. SUBJECTS: The sample included 24 participants scoring between 20 and 24 on the AMMSE. Demographic characteristics of the sample included an age range from 60 to 80, with 67% female, 46% American Indian, and the remainder white. INTERVENTIONS: Twelve participants were exposed to 4 weeks of weekly treatments of Reiki from two Reiki Master-level practitioners; 12 participants served as controls and received no treatment. OUTCOME MEASURES: The two groups were compared on pre- and post-treatment scores on the AMMSE and the Revised Memory and Behavior Problems Checklist (RMBPC). RESULTS: Results indicated statistically significant increases in mental functioning (as demonstrated by improved scores of the AMMSE) and memory and behavior problems (as measured by the RMBPC) after Reiki treatment. This research adds to a very sparse database from empirical studies on Reiki results. CONCLUSION: The results indicate that Reiki treatments show promise for improving certain behavior and memory problems in patients with mild cognitive impairment or mild Alzheimer's disease. Caregivers can administer Reiki at little or no cost, resulting in significant societal value by potentially reducing the needs for medication and hospitalization.     

Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment

In this study we used magnetoencephalography during a modified version of the Sternberg's memory recognition task performed by patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event-related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline.     

Multimodal classification of Alzheimer's disease and mild cognitive impairment

Effective and accurate diagnosis of Alzheimer's disease (AD), as well as its prodromal stage (i.e., mild cognitive impairment (MCI)), has attracted more and more attention recently. So far, multiple biomarkers have been shown to be sensitive to the diagnosis of AD and MCI, i.e., structural MR imaging (MRI) for brain atrophy measurement, functional imaging (e.g., FDG-PET) for hypometabolism quantification, and cerebrospinal fluid (CSF) for quantification of specific proteins. However, most existing research focuses on only a single modality of biomarkers for diagnosis of AD and MCI, although recent studies have shown that different biomarkers may provide complementary information for the diagnosis of AD and MCI. In this paper, we propose to combine three modalities of biomarkers, i.e., MRI, FDG-PET, and CSF biomarkers, to discriminate between AD (or MCI) and healthy controls, using a kernel combination method. Specifically, ADNI baseline MRI, FDG-PET, and CSF data from 51AD patients, 99 MCI patients (including 43 MCI converters who had converted to AD within 18 months and 56 MCI non-converters who had not converted to AD within 18 months), and 52 healthy controls are used for development and validation of our proposed multimodal classification method. In particular, for each MR or FDG-PET image, 93 volumetric features are extracted from the 93 regions of interest (ROIs), automatically labeled by an atlas warping algorithm. For CSF biomarkers, their original values are directly used as features. Then, a linear support vector machine (SVM) is adopted to evaluate the classification accuracy, using a 10-fold cross-validation. As a result, for classifying AD from healthy controls, we achieve a classification accuracy of 93.2% (with a sensitivity of 93% and a specificity of 93.3%) when combining all three modalities of biomarkers, and only 86.5% when using even the best individual modality of biomarkers. Similarly, for classifying MCI from healthy controls, we achieve a classification accuracy of 76.4% (with a sensitivity of 81.8% and a specificity of 66%) for our combined method, and only 72% even using the best individual modality of biomarkers. Further analysis on MCI sensitivity of our combined method indicates that 91.5% of MCI converters and 73.4% of MCI non-converters are correctly classified. Moreover, we also evaluate the classification performance when employing a feature selection method to select the most discriminative MR and FDG-PET features. Again, our combined method shows considerably better performance, compared to the case of using an individual modality of biomarkers.     

Automatic morphometry in Alzheimer's disease and mild cognitive impairment

This paper presents a novel, publicly available repository of anatomically segmented brain images of healthy subjects as well as patients with mild cognitive impairment and Alzheimer's disease. The underlying magnetic resonance images have been obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. T1-weighted screening and baseline images (1.5T and 3T) have been processed with the multi-atlas based MAPER procedure, resulting in labels for 83 regions covering the whole brain in 816 subjects. Selected segmentations were subjected to visual assessment. The segmentations are self-consistent, as evidenced by strong agreement between segmentations of paired images acquired at different field strengths (Jaccard coefficient: 0.802±0.0146). Morphometric comparisons between diagnostic groups (normal; stable mild cognitive impairment; mild cognitive impairment with progression to Alzheimer's disease; Alzheimer's disease) showed highly significant group differences for individual regions, the majority of which were located in the temporal lobe. Additionally, significant effects were seen in the parietal lobe. Increased left/right asymmetry was found in posterior cortical regions. An automatically derived white-matter hypointensities index was found to be a suitable means of quantifying white-matter disease. This repository of segmentations is a potentially valuable resource to researchers working with ADNI data.     

Antioxidant treatment prevented late memory impairment in an animal model of sepsis

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.     

Potential therapeutic action of natural products from traditional Chinese medicine on Alzheimer's disease animal models targeting neurotrophic factors

Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells leads to memory loss and cognitive decline. To reduce the death rate and improve the biological activity of neurocytes, neurotrophic factors (NTFs) exhibit therapeutic effect on AD. However, therapeutic application of exogenous NTFs in treatment of AD is largely limited due to short half‐life, poor stability, etc. Various extracts of traditional Chinese medicine (TCM) have been shown to exhibit therapeutic effects on AD, and some of these effects are associated with regulation on the expression of nerve growth factor, brain‐derived neurotrophic factor (BDNF), and glial cell line‐derived neurotrophic factor (GDNF) and their associated receptors. This article reviews the progress on promotion of Panax ginseng, Rehmannia glutinosa Libosch., Epimedium, Polygala tenuifolia Willd, and seven other TCMs on secretion of NTFs during AD, with a view to preparation development and clinical application of these TCMs on AD.     

Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease

Increasing evidence suggests that the elevation of beta-amyloid (Abeta) peptides in the brain is central to the pathogenesis of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, enhances cAMP/protein kinase A/extracellular signal-regulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons and ameliorates Abeta-induced memory impairment in AD model rats. For the first time, we report that this natural compound improves memory deficits in amyloid precursor protein (APP) transgenic mice that overexpress human APP695 harboring the double Swedish and London mutations [APP-SL 7-5 transgenic (Tg) mice]. Our enzyme-linked immunosorbent assay (ELISA) also showed that administration of nobiletin to the transgenic mice for 4 months markedly reduced quantity of guanidine-soluble Abeta(1-40) and Abeta(1-42) in the brain. Furthermore, consistent with the results of ELISA, by immunohistochemistry with anti-Abeta antibody, it was evidently shown that the administration of nobiletin decreased the Abeta burden and plaques in the hippocampus of APP-SL 7-5 Tg mice. These findings suggest that this natural compound has potential to become a novel drug for fundamental treatment of AD.     

Atlas-based hippocampus segmentation in Alzheimer's disease and mild cognitive impairment

This study assesses the performance of public-domain automated methodologies for MRI-based segmentation of the hippocampus in elderly subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Structural MR images of 54 age- and gender-matched healthy elderly individuals, subjects with probable AD, and subjects with MCI were collected at the University of Pittsburgh Alzheimer's Disease Research Center. Hippocampi in subject images were automatically segmented by using AIR, SPM, FLIRT, and the fully deformable method of Chen to align the images to the Harvard atlas, MNI atlas, and randomly selected, manually labeled subject images ("cohort atlases"). Mixed-effects statistical models analyzed the effects of side of the brain, disease state, registration method, choice of atlas, and manual tracing protocol on the spatial overlap between automated segmentations and expert manual segmentations. Registration methods that produced higher degrees of geometric deformation produced automated segmentations with higher agreement with manual segmentations. Side of the brain, presence of AD, choice of reference image, and manual tracing protocol were also significant factors contributing to automated segmentation performance. Fully automated techniques can be competitive with human raters on this difficult segmentation task, but a rigorous statistical analysis shows that a variety of methodological factors must be carefully considered to insure that automated methods perform well in practice. The use of fully deformable registration methods, cohort atlases, and user-defined manual tracings are recommended for highest performance in fully automated hippocampus segmentation.     

Declarative memory impairments in Alzheimer's disease and semantic dementia

Semantic dementia (SD) and Alzheimer's disease (AD) are both disorders in which early pathology affects the temporal lobe yet they produce distinct syndromes of declarative memory impairment-loss of established semantic knowledge with relatively preserved episodic memory in the former and the converse in the latter. Groups with mild SD and mild AD who showed a double dissociation in these two aspects of declarative memory were studied-the SD group's episodic memory and the AD group's semantic knowledge each being comparable to controls. Positron emission tomography and volumetric magnetic resonance imaging were used to map deficits in regional cerebral metabolic rate and mesial temporal lobe (MTL) atrophy, respectively. Episodic memory impairment in AD was associated with dysfunction of an integrated network (mesial temporal lobe, mamillary bodies, dorso-mesial thalamus and posterior cingulate). Semantic memory impairment in SD was associated with bilateral rostral temporal lobe hypometabolism. The SD group had comparable MTL atrophy and hypometabolism to that found in AD but the remainder of their limbic-diencephalic network was preserved suggesting that the latter explains their ability to acquire new episodic memories. The results challenge the view that amnesia in early AD can be explained by the degree of MTL damage alone while showing that semantic impairment can occur with damage restricted to the rostral temporal lobes.     

中期帕金森病患者视觉空间工作记忆研究

目的:探讨中期帕金森病(PD)患者的视觉空间工作记忆损害及其特点。方法:采用自行修订的Smith工作记忆检查软件,对临床确诊的中期PD患者组和对照组进行视觉空间工作记忆检查。结果:PD组(26例)患者的视觉空间距离工作记忆检查成绩(76．19±11．95)%较对照组(26例)(82．42±8．35)%显著下降,且差异有统计学意义(t=-2．179,P=0．034);PD组患者视觉空间位置工作记忆检查成绩(94．46±11．75)%与对照组(96．88±3．55)%的差异无统计学意义(t=-1．007,P=-0．319)。而起病于右侧肢体的患者视觉空间距离工作记忆的成绩较对照组下降,且差异有统计学意义(t=-3．142,P=-0．003)。结论:中期PD患者存在视觉空间距离工作记忆的损害,而视觉空间位置工作记忆相对保留,提示距离和位置工作记忆加工应用不同的神经环路。     

阿尔茨海默病情绪记忆相关脑灰质体积改变

目的 探讨阿尔茨海默病（AD）患者情绪记忆改变与灰质容积变化的相关性。方法 对25例AD患者（AD组）及25名正常对照（NC组）进行情绪记忆行为学检测,获取行为学成绩。采用MRI 3D结构相用VBM8和SPM8软件处理,得到相对灰质体积改变的脑区,做为ROI,采用REST软件提值,并与行为学成绩行相关性分析。结果 AD组受试对负性与中性图片反应正确率差异无统计学意义（P=0.56）。与NC组比较,AD组灰质体积缩小的脑区包括双侧颞下回、颞中回、海马、海马旁回、杏仁核、梭状回、楔前叶、后扣带回、左侧脑岛、右侧舌回、左侧额叶眶内侧回、左侧内侧前额叶、右侧额下回岛盖部、左侧中央前回及右侧丘脑（FWE校正,P<0.025）;其中双侧杏仁核、双侧后扣带回、左侧海马、左侧脑岛、左侧颞下回、左侧颞中回、左侧额叶眶内侧回、右侧额下回岛盖部、左侧内侧前额叶的相对灰质体积与情绪图片记忆反应正确率呈正相关（P均<0.05）。结论 AD患者负性图片情绪增强效应损害,可能与杏仁核和海马等情绪记忆系统脑区萎缩有关。     

帕金森病模型大鼠的学习记忆功能障碍

目的:利用Morris水迷宫对帕金森病模型大鼠的学习记忆障碍进行分析评价,为帕金森病的早期诊断及记忆障碍的治疗提供依据。方法:实验于2004-05/2005-04在安徽省立医院神经干细胞移植实验室及安徽医科大学神经生物学教研室完成。①筛选:制作帕金森病模型之前淘汰有记忆障碍的大鼠及有旋转行为的大鼠。②模型制备:采用立体定向技术建立6-羟多巴诱发的帕金森病大鼠模型。③检测指标:通过Morris水迷宫实验测定模型1个月时及3个月时大鼠寻找平台潜伏期、游泳距离、游泳速度、120s内在各象限游泳距离占总距离百分比。结果:共纳入实验大鼠74只,①淘汰了有记忆障碍、游泳时原地转圈及不成功模型共33只。最后纳入实验41只大鼠。帕金森病模型1个月组15只,帕金森病模型3个月组16只,对照组10只。②对照组大鼠与帕金森病模型1个月组大鼠游泳速度比较差异存在显著性(P<0.05)。帕金森病模型1个月组与3个月组比较差异不显著(P>0.05)。③帕金森病模型大鼠游泳距离明显增加,与对照组比较差异显著(P<0.05)。④对照组平台象限的距离与其他象限比较差异显著(P<0.05)。帕金森病模型1,3个月组各象限的游泳距离比较差异无显著性。结论:帕金森病模型大鼠表现出渐进的空间记忆能力和搜索策略的损害,与早期帕金森病患者表现的工作记忆损害相似。